In this study, the authors explored the therapeutic effect of glycyrrhizin (GL) on Coxsackievirus B3 (CVB3)-induced myocarditis and its possible mechanisms involved. The results of this study showed that GL exhibited a profound amelioration of CVB3-induced myocarditis, as evidenced by improved weight loss profile, less increased serological levels of cardiac enzymes, less myocardial inflammation and increased survival rate. Further study showed that this effect was not due to the viral clearance but ascribed to weakened proinflammatory responses, as evidenced by significantly reduced expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β and interleukin-6. Moreover, the authors demonstrated that GL administration inhibited CVB3-induced nuclear factor-κB activity efficiently by blocking the degradation of nuclear factor -κB inhibitor IκBκ. These data suggest that GL can effectively attenuate the severity of CVB3-induced myocarditis and may present as a new therapeutic approach for the treatment of viral myocarditis.